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SOE 577: Thyroid Physiology 2

Introduction

Regarding the thyroid gland…

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Question No. 2

Q: Describe the microscopic structure of the thyroid gland?

Answer No. 2

  • Functional unit of the thyroid is the follicle:
    • Outer sphere of cuboidal epithelial cells (thyrocytes) and thin basement membrane:
      • Site of thyroglobulin production
    • Filled with a protein rich core called colloid:
      • Made up of thyroglobulin a large glycoprotein
      • Serves as the main storage of thyroid hormones
  • C-cells are dispersed between follicles to produce calcitonin
Microscopic structure of the thyroid gland showing thyroid follicles

Question No. 3

Q: Which hormones are produced by the thyroid gland?

Answer No. 3

Hormone
Function
Thyroxine (T4) - carries 4 iodine atoms)
Regulation of metabolism and growth
Triiodothyronine (T3) - carries 3 iodine atoms)
Regulation of metabolism and growth
Reverse-triiodothyronine (r-T3) - formed by peripheral conversion of T3
Metabolically inactive
Calcitonin
Regulation of calcium and phosphate levels (lowers serum levels through deposition in bone and renal excretion)

Question No. 4

Q: What are the functions of thyroid hormone (T3 & T4)?

Answer No. 4

Effects on Metabolism
  • Increase basal metabolic rate of most tissues (Long duration of action):
    • Increased heat production
    • Increases cardiac metabolic rate:
      • Ionotropic / chronotropic effect
    • Increased lipolysis & gluconeogenesis
Effect on Beta Receptors
  • Increases number and sensitivity of B adrenoceptors
    • Sensitises catecholamines
    • Sensitises effects of insulin
  • Increase in heart rate (HR) and myocardial contractility leading to an increase in cardiac output
Effect on Growth and Development
  • Increases Growth hormone
  • Vital in growth and development of nervous system:
    • Neuronal myelination
    • Nerve axon growth

Question No. 5

Q: Compare T3 and T4?

Answer No. 5

T3
  • Active form of thyroid hormone - 3x more potent than T4
  • 20% of T3 secreted directly from the thyroid
  • 80% converted peripherally from T4
T4
  • Often referred to as the prohormone due to low biological coactivity
  • Approximately 90% is converted in peripheral tissues to more active T3 form - principally in the liver and kidneys
  • Can also be converted to metabolically inactive reverse T3 (rT3)
    • Fasting increases the ratio of rT3:T3.

Question No. 6

Q: How is thyroid hormone (T3 & T4) synthesised, stored and released?

Answer No. 6

Can be considered in 4 steps:

1. Iodide Trapping
  • Iodine obtained in diet from dairy, grains and meat (150mg/day required)
  • Reduced to the inorganic form iodide (I-)
  • Actively taken up by thyroid follicular cells, stimulated by TSH:
    • Transported against a concentration gradient by Na+/I- Symporter (NIS)
2. Iodide Oxidation & Organification
  • Moves apically in the cell where is oxidised to iodine (I+)
  • Requires the membrane bound enzyme thyroperoxidase
  • I+ covalently binds to tyrosine residues on thyroglobulin in the colloid
  • May be iodinated at one or two positions forming:
    • Monoiodotyrosine (MIT)
    • Diiodotyrosine (DIT)
3. Storage in Colloid with Thyroglobulin
  • Tyrosine residues couple to form precursors of thryroid hormones:
    • MIT & DIT couple to form T3
    • DIT & DIT couple to from T4
  • T3 & T4 remain attached to the thyroglobulin molecule for storage in colloid
4. Secretion of Thyroid Hormones
  • When stimulated by TSH, thyroglobulin is internalised into the thyrocyte membrane via endocytosis
  • Lysosomal endopeptidase cleaves the thyroglobulin releasing T3 and T4
  • Thyroid hormones are released into the cytoplasm and diffuse into the bloodstream through the basement membrane
Thyroid hormone formation, synthesis and release

Question No. 7

Q: How is thyroid hormone transported?

Answer No. 7

  • <1% transported freely in plasma unbound to plasma proteins:
    • Forms the active portion of the hormone
  • Mostly transported by non-covalent binding to plasma proteins:
    • Thyroid binding globulin (TBG) - predominant transport protein
    • Transthyretin
    • Albumin
  • TBG has 10x the affinity for T4 than T3:
    • Therefore T3 is more readily available and is removed from the circulation

Question No. 8

Q: What factors control the synthesis and secretion of thyroid hormone?

Answer No. 8

  • Thyroid hormone production is regulated by a series of negative feedback loops
  • Thyroid stimulating hormone (TSH) is an important regulator:
    • Peptide hormone produced in the anterior pituitary gland
    • Stimulates the production and release of thyroid hormones
    • TSH production is stimulated by:
      • TRH production
      • Low serum levels of thyroid hormones
    • TSH production is inhibited by:
      • High serum levels of thyroid hormones (negative feedback loop)
      • High serum levels of TSH (ultra-short negative feedback loop)
  • Thyrotropin-releasing hormone (TRH) is another important regulator:
    • Peptide hormone produce in the hypothalamus
    • Stimulates the production and release of TSH
    • TRH production is stimulated by:
      • Low serum levels of thyroid hormones
    • TRH production is inhibited by:
      • High serum levels of thyroid hormones (negative feedback loop)
Regulation of thyroid hormone release by the hypothalamus and pituitary glands

Question No. 9

Q: What is a portal circulation?

Answer No. 9

An arrangement by which blood passes from one set of capillaries, through a large vessel or vessels, to another set of capillaries before returning to the systemic circulation

Basic structure of a portal system with two capillary beds

Question No. 10

Q: Where do portal circulations exist in the body?

Answer No. 10

Three portal systems exist within the body:

  • Hypothalamus & anterior pituitary gland
  • Liver
  • Kidneys (nephrons)

Question No. 11

Q: Why is the hypothalamic-pituitary axis a portal circulation?

Answer No. 11

Hypothalamus & Anterior Pituitary
  • Blood vessels enter the hypothalamus and form a capillary network into which trophic releasing hormones are released
  • Portal vessels communicate with the anterior pituitary gland providing a method of hormonal communication
  • A second capillary network allows the action of trophic releasing hormones on pituitary cells and the subsequent release of organ specific hormones which are distributed around the body

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